Targeting endothelial tPA-dependent NMDAR signaling with Glunomab increases the benefit of rtPA-mediated thrombolysis in nonhyperglycemic mice. (A) Schematic representation of the experimental protocol. (B) Quantification of ischemic lesion volume, 24 hours after MCAo assessed by T2-weighted imaging (7T MRI) in mice treated with saline (vehicle group), rtPA (10 mg/kg; Actilyse, 10% bolus, 90% perfusion during 40 minutes; rtPA group), Glunomab (300 μg, 100% bolus; Gluno group), or a combination of Glunomab-rtPA (Gluno-rtPA group). Individual values, means and SEM are plotted. 21.57 mm³ for vehicle group (n = 12); 12.07 mm³ for tPA group (n = 12); 10.26 mm³ for Gluno group (n = 12); and 11.04 mm³ for Gluno-rtPA group (n = 12). Ordinary 1-way ANOVA (P < .001); Tukey test for multiple comparisons (∗P < .05 and ∗∗P < .01). (C) Percentage of angiographic scores, 24 hours after MCAo assessed by FLASH_TOF_2D imaging (7T MRI) in vehicle, rtPA, Gluno, and Gluno-rtPA groups (n = 12 per group). No recanalization = complete occlusion (orange); partial recanalization = incomplete filling of the distal bed (light green); and complete recanalization = complete filling of the distal bed (dark green). Kruskal-Wallis test (P = .33). (D) Proportion of HT per group, 24 hours after MCAo assessed by T2∗-weighted imaging (deoxyhemoglobin; 7T MRI) in vehicle, rtPA, Gluno, and Gluno-rtPA groups (n = 12 per group). Fisher exact tests between groups (P > .05).